Objective   To study the effects of 7week treadmill exercise combined with black lycium polysaccharide on depression-like behaviors and explore the alterations of hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor （AMPAR）associated pathways in mice.  Methods   Fifty male Kunming (KM) mice were randomly divided into blank group (K, n=10) and chronic unpredictable mild stress group（CUMS, n=40）. For the CUMS group, 13 random chronic unpredictable mild stress method  were used to induce depression-like behaviors. After successful modeling, the mice were further divided into model group (M), treadmill exercise group (E), black lycium polysaccharide group (L), and treadmill exercise combined with black lycium polysaccharide group (EL); each group contained 10 mice, and intervention lasted for 7 weeks. The behavioral assessment was performed; the contents of 5-hydroxytryptamine（5-HT）, brain-derived neurotrophic factor (BDNF) and dopamine (DA) in hippocampal tissue, and the levels of S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE）in serum were detected; Nissl staining was carried out to observe the structure of brain tissue; AMPAR, glutamate receptor 1(GluR1) and calcium/calmodulin-dependent protein kinase α (CaMKⅡα) proteins in hippocampal tissue were detected; Real-time PCR was used to verify the expression of hippocampal AMPAR, GluR1 and CaMKⅡα mRNA obtained by mRNA sequencing.  Results   1. Compared with the blank group, the mice in CUMS group had obvious depression-like behaviors (P<0.01); the contents of 5-HT, BDNF and DA in hippocampal tissue decreased significantly, while those of S100B and NSE increased (P<0.01); Neurons in the prefrontal cortex were absent, the Nissl nacleus was condensed, and the arrangement was irregular and sparse. 2. Compared with the model group, the behavioral assessment of the mice in the E, L and EL groups were significantly improved, reflecting that the contents of 5-HT, BDNF and DA in hippocampal tissue increased, and the serous S100B and NSE levels decreased (P<0.01 or P<0.05); for sucrose preference test (SPT) and forced swimming test (FST), S100B and NSE content result  showed that treadmill exercise and black lycium polysaccharide intervention had a synergistic effect on behavioral improvement. 3. Compared with the model group, the contents of AMPAR, GluR1, and CaMKⅡα proteins in hippocampal tissue of mice in the E, L and EL groups increased (P<0.01), and there was a synergistic effect between treadmill exercise and black lycium polysaccharides; the Illumina high-throughput sequencing data showed that there were 49 upregulated genes and 18 down-regulated genes involving learning and memory, and neuronal damage repair, etc. which were closely related to postsynaptic membrane location of AMPA receptors and synaptic long-term potentiation and long-term depression, The increased transcriptions of AMPAR, GluR1 and CaMKⅡα revealed by the sequencing were verified by Real-time PCR data, and there was a synergistic effect between the treatments of treadmill exercise and black lycium polysaccharides.  Conclusion   Seven weeks of treadmill exercise and administration of black lycium polysaccharides can improve depression-like behaviors in mice, possibly by affecting the phosphorylation of CaMKⅡα to regulate AMPAR activity, promote neuronal damage repair and improve synaptic plasticity and function.

There are a variety of mechanical signals in the microenvironment of cells, which have temporal and spatial variability, which jointly regulate the histological processes such as cell proliferation, differentiation and migration. Piezo1 is a mechanically sensitive cationic channel. As a force sensor, it transmits signals to downstream pathways and participates in a variety of life activities in response to changes in the cell microenvironment. In this paper, the common signal pathways of Piezo1 were reviewed in order to identify the downstream signaling pathways regulated by Piezo1, thereby providing theoretical basis for inhibiting or delaying related diseases.

 Tumor is the main lethal type of major diseases that human beings are facing nowadays. Traditional therapies, such as chemotherapy, surgery, radiotherapy, etc, have been the mainstay of tumor treatment for a long time, and still have their own limitations in terms of effectiveness. In recent years, immunotherapy for tumors has attracted much attention with the rise of strategies such as immune checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) relay therapy, and anti-tumor vaccines. Among them, CAR-T cell therapy, as a breakthrough tumor immunotherapy method, can precisely target tumors at the cellular and molecular levels by modifying the patient’s own T cells to express recombinant antigen receptors targeting specific tumor antigens, breaking the restriction of the major histocompatibility complex (MHC) of the natural T cells themselves. It can precisely target tumors at the cellular and molecular levels, and thus can efficiently and specifically identify and kill cancer cells, providing a new perspective for treatment. Since the approval of the first CAR-T therapy by the US Food and Drug Administration (FDA) in 2017, in addition to still maintaining significant advantages in the field of classical multiple hematologic malignancies, it has also made outstanding progress in the treatment and clinical trials of some solid tumors and autoimmune diseases, among others. This paper  will briefly review the current principles, applications, challenges and directions of development of CAR-T technology. 

Objective   To investigate the effect of microplastic (MPs) exposure on learning and memory in mice, and its mechanism by observing the protein expression of brain-derived neurotrophic factor (BDNF) /tyrosine receptor kinase B (TrkB) /N-methyl-D-aspartate receptor subtype 2B (NR2B) signaling pathway and neurogenesis.  Methods  Forty male C57BL/6 mice were randomly divided into control group (Ctrl) and microplastics exposure group (MPs). Mice in MPs group were treated with 0.3 mg/(kg·d) microplastics, administered by gavage at a volume of 200 μl for 30 consecutive days. Morris water maze test was used to evaluate the spatial learning and memory ability of mice. Western blotting was used to detect the protein levels of BDNF, TrkB and NR2B in hippocampus of mice. Immunofluorescent staining was used to observe the number of doublecortin (DCX) and neuronal nuclei antigen (NeuN) positive cells in the hippocampus of mice to evaluate hippocampal neurogenesis.  Results  Compared with the control group, the ability of learning and memory decreased significantly in MPs group mice (P<0.01). The expression levels of BDNF, TrkB and NR2B in the hippocampus of MPs group mice were significantly lower than those of control group (P<0.05). The number of DCX and NeuN positive cells in the hippocampus of MPs group was significantly lower than that of control group (P<0.01).  Conclusion   MPs exposure induces learning and memory impairment which may be related to inhibiting BDNF/TrkB/NR2B signaling pathway and reducing hippocampal neurogenesis. 

Epilepsy is a common chronic neurological disorder caused by abnormal electrical activity in the brain, and its pathogenesis has not been fully clarified. In recent years, more and more studies have shown that iron, zinc and copper in the brain are involved in the occurrence and development of epilepsy. These metal ions possibly play a role in epileptogenesis by affecting neuronal excitability and signal transduction through alterating ion channel function, potential balance, action potential propagation, redox and so on. In this review, we mainly analyse the effects of these metal ions on epilepsy, in order to explore the underlying mechanisms of epilepsy and provide promising therapeutic strategies for epilepsy based on metal ions. 

Objective   To explore the mechanism of Angelica Sinensis polysaccharide (ASP) promoting donor bone marrow transplantation (BMT) to reconstruct hematopoietic function of receptor mice by regulating bone marrow stromalcells (BMSCs).  Methods   Bone marrow mononuclear cells (BMMNCs) of male C57BL/6J mice aged 8-10 weeks were separated, purified and transplanted into female receptor mice of the same age. On the ninth day, receptor mice BMMNCs were separated, purified and transplanted again into female receptor mice. The transplanted receptor mice were divided into control group:  sham irradiation; Irradiation(IR) group: a whole-body irradiation with a total dose of 8.0 Gy X-ray; BMT group: the receptor mice treated in the same way as the IR group and transplanted BMMNCs (5×106 cells) from male donor via the tail vein; BMT+ASP group: the receptor mice treated in the same way as the BMT group, and injected ASP ［100 mg/（kg·d）×9］ by intraperitoneal route from the first day of transplantation. Changes in body weight and survival rate of mice were recorded during modeling, receptor mice BMMNCs were collected to detect sexdetermining region of Y(SRY) gene after building model, peripheral blood indexes, the number of BMMNCs in femur and histopathology of bone marrow were detected; BMSCs in receptor mice was separated and purified, BMSCs adhesion ability was observed, proliferation ability was detected by 5-ethynyl-2-deoxyuridine(EdU);The level of reactive oxygen species (ROS), the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in BMSCs were detected; The levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor(SCF), insulinlike growth factor 1(IGF-1) in culture supernatant of BMSCs were determined, CFU-Mix was counted after BMMNCs co-cultured with receptor BMSCs in each group for 48 hours;The expression of Notch signaling pathway related genes (Notch1, Jagged1, Hes1) in BMMNCs were measured by Real-time PCR.    Results   All mice in IR group were died,the body weight loss in BMT+ASP group was not obvious. The SRY gene was detected in the receptor female mice BMMNCs. Peripheral blood indexes and the number of BMMNCs were not significantly decreased in BMT+ASP group receptor mice,and bone marrow histopathological injury was reduced. ASP promoted the proliferation of BMSCs, decreased the contents of ROS and MDA, and increased the activity of SOD in BMSCs. ASP promoted the secretion of SCF, GM-CSF and IGF-1 in BMSCs, and increased CFU-Mix yield of BMMNCs co-cultured with receptor BMSCs. ASP increased the expression of Notch1, Jagged1 and Hes1 mRNA in BMMNCs.  Conclusion   The mechanism of ASP promoting receptor hematopoietic function reconstruction is related to reducing the oxidative stress damage of hematopoietic microenvironment, improving the secretion of hematopoietic growth factors in BMSCs, and regulating Notch signaling pathway. 

Objective  To explore the common features of Chinese ethnic groups.  Methods   Eight body indexes of 62 ethnic groups in China were analyzed.  Results   The cluster analysis showed that 52 males and 59 females ethnic groups were grouped into the mixed group dominated by the northern ethnic group and the mixed group dominated by the southern ethnic group. Eight Han ethnic groups were grouped into each group, but no Han group was aggregated. The result  of body index classification showed that the main body types of Chinese male population were long trunk, middle chest, wide shoulder, wide pelvis and middle leg. Middle body, wide chest, wide shoulder, wide pelvis and middle leg were the main body types of Chinese female population. This showed that the characteristics of Chinese ethnic groups had obvious consistency. The consistency of Chinese group features was related to its close origin. It should be said that Han nationality played an important role in the process of communication and integration of various ethnic groups in China. In the history of the Han nationality, there had been many large-scale population migration. The southern movement of the northern ethnic minorities into the northern Han and the southward movement of the northern Han into the south promoted the formation of the Southern Han, which made the southern Han and the northern Han had similar body features, and also promoted the southern ethnic minorities into the southern Han. In addition, the Han nationality who moved into minority areas also gradually integrated into minority areas. Conclusion   There are obvious commonalities in Chinese ethnic groups. 

Objective  To explore the distribution and localization of dopamine receptor D3-D5 in the small intestine of different species.  Methods   The distribution and expression of D3-D5 in the small intestine of mice, rats and rhesus monkeys were detected by immunohistochemistry and Western blotting. The expression of D3-D5 in immunoglobulin A positive plasma cells (IgA+PC) located in the lamina propria (LP) were detected by immunofluorescence double labeling.  Results   D3 and D5 were widely distributed in the epithelium, LP, submucosal plexus (SMP) and intermuscular plexus (MP) of the small intestine in mice, rats and rhesus monkeys. The distribution of D4 in the small intestinal of mice and rhesus monkeys were consistent with the result  of D3 and D5. D4 was distributed only within the epithelium and LP of rat small intestine. D3 and D5 were expressed in the IgA+PC in the LP of mice and rats, whereas D4 was not.  Conclusion  The distribution and localization pattern of D3 and D5 are similar in the small intestine of mice, rats and rhesus monkeys, whereas those of D4 vary between different species. Dopamine may be involved in regulating the functions of IgA+PC. 

Objective   To observe the effect of electric stimulation on nuclear factor-κB (NF-κB)/ NOD-like receptor protein 3 (NLRP3) signaling pathway and microglial cell morphology in mice with lipopolysaccharide（LPS）induced chronic neuroinflammation, and to explore the protective mechanism of electric stimulation on brain of mice.  Methods   C57BL/6 mice were randomly divided into blank control group (n=8), model group (n=12), sham electroacupuncture group (n=6) and electroacupuncture group (n=6). Except blank control group, mice in other groups were injected intraperitoneally with LPS (0.25mg/kg) for 7 consecutive days. On the 8th day, mice in the sham electroacupuncture group and electroacupuncture group were treated with acupuncture or Zusanli electroacupuncture for 7 consecutive days. The mice were weighed before the experiment, on the 7th and 14th days. On the 13th day, the elevated cross maze test was performed on the mice. The open field test was performed on the 14th day. After the experiment, immunofluorescence assay was used to determine the expression of microglial ionized calcium binding adaptor molecule-1(Iba-1) in prefrontal cortex region. The mRNA expression of NF-κB, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), Caspase-1 and interleukin (IL)-18 were detected by Real-time PCR. The protein expression levels of NF-κB, iNOS, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, IL-1β and IL-18 were detected by Western blotting.  Results   Weight change, On the 7th day, compared with the control group, the body weight of mice in model group, sham electroacupuncture group and electroacupuncture group decreased (P<0.0001), respectively; On the 14th day, compared with the control group, the weight of mice in the model group decreased (P<0.0001); Compared with the sham electroacupuncture group, the body weight of mice in the electroacupuncture group increased (P<0.05). Elevated cross maze experiment, compared with the control group, the total distance and open arm retention time of mice in model group decreased, while the closed arm retention time increased (P<0.05). The open field experiment showed that compared with the control group, the model group mice showed a decrease in total distance traveled, slower movement speed, and fewer entries into the central area(P<0.001); Compared with the model group, the electroacupuncture group showed an increase in all three indicators(P<0.01); Compared with the sham electroacupuncture group, the total distance and motion speed of mice in electroacupuncture group both increased (P<0.05). Immunofluorescence assay, compared with the control group, the relative fluorescence of Iba-1 in prefrontal cortex area of mice in model group increased (P<0.05). Compared with the model and sham electroacupuncture group, the relative fluorescence of Iba-1 in prefrontal cortex area of mice in electroacupuncture group decreased (P<0.05). Real-time PCR showed that compared with the control group, mRNA expressions of NF-κB, iNOS, TNF-α, Caspase-1 and IL-18 in the model group increased (P<0.05); Compared with the model group, mRNA expressions of NF-κB, iNOS, TNF-α, Caspase-1 and IL-18 in electroacupuncture group decreased (P<0.05). Western blotting indicated that compared with the control group, the protein expressions of NF-κB, iNOS, Caspase-1, IL-1β and IL-18 in model group increased (P<0.05); Compared with model group, the protein expressions of NF-κB, iNOS, NLRP3, ASC, Caspase-1, IL-1β and IL-18 in electroacupuncture group decreased (P<0.05); Compared with the sham electroacupuncture group, IL-18 protein in electroacupuncture group decreased (P<0.05).  Conclusion   Electroacupuncture can improve the behavioral performance of mice and inhibit the activation of microglia in the cortical region of mice, which may play an anti-inflammatory and protective role by regulating NF-κB/ NLRP3 pathway. 

Ovarian cancer is one of the most common gynecologic cancers in the world. Over the past few decades, there has been considerable research reporting on the mechanisms of cancer development and progression, with multiple nerve as well as neurotransmitters involved. Nerve innervation is also found in ovarian cancer. And in ovarian cancer, various nerves and neurotransmitters play different roles. They are involved in ovarian cancer cells’ proliferation metastasis, apoptosis and changes in the tumor microenvironment. Further understanding of the role of these nerve endings in the development of ovarian cancer is essential for understanding the mechanisms of cancer progression. This will be important for subsequent research focusing on tumor regulation. While glucocorticoids and sympathetic nerve-released norepinephrine are able to promote ovarian cancer progression, serotonin may inhibit cancer cell growth. Also, parasympathetic and sensory nerves are capable of having either a positive or negative effect on ovarian tumors. These relevant studies offer the possibility of new therapeutic options for oncology, it may be possible to mitigate the progression of cancer with inexpensive receptor inhibitors or agonists. This will facilitate the subsequent exploration of therapeutic possibilities forovarian cancer and other cancer-related treatments. In this review, we also present some insights into the role of the nervous system in the regulation of ovarian cancer, which we hope will provide new insights into the innervation and progression of ovarian cancer. 

Objective To investigate the antitumor effects of triptolide against CT26 colon cancer and its impact on the expression of Polo-like kinase-1 (PLK-1) protein.  Methods  Forty clean grade BALB/c mice, each mouse was implanted with 1×10⁶ CT26 cells into the dorsal side of the right forelimb to establish a tumor-bearing mouse model. Experimental animals were randomly divided into four groups, the tumor model group (saline control), the positive drug group ［oxaliplatin, 5mg/(kg·d)］, the low-dose triptolide group ［50μg/(kg·/d)］, and the high-dose triptolide group ［100μg/(kg·d)］. The drugs were administered through intraperitoneal injection (10 times in total, once every other day). The in vitro effects of the drugs on the proliferation, migration, invasion, and mitosis of CT26 cells were also assessed.   Results  Triptolide significantly inhibited the proliferation, migration, and invasion of CT26 colon cancer cells, and disrupted the separation of centrosomes and the correct arrangement of chromosomes during the prophase of mitosis in tumor cells. The binding energy of triptolide and PLK-1 protein was -7.1 kcal/mol, and it could down-regulate the expression of PLK-1 in CT26 cells.  Conclusion  Triptolide exerts its antitumor effects against CT26 colon cancer by downregulating the expression of PLK-1.

Objective  To survey and analysis of cephalometric indicators of Wa adults in China.  Methods  Cephalometric parameters were measured in 1996 cases (858 males and 1138 females) of Wa adults in China, including 927 cases (381 males and 546 females) of the Baraoke ethnic group, 564 cases (241 males and 323 females)of the A Wa ethnic group, and 505 cases (236 males and 269 females) of the Wa ethnic group by using sliding caliper and spreading caliper. Seventeen direct cephalofacial parameters and one indirect parameter for each of the three dialect ethnic groups were derived separately and analyzed for age correlations, inter-sex u-tests,and multiple comparisons. Finally, the three dialect ethnic groups were subjected to cluster analysis and principal component analysis with 15 ethnic groups in China.  Results   Nose breadth, mouth breadth and physiognomic ear length were significantly and positively correlated with age for both sexes in the three Wa dialect ethnic groups, while head breadth and lip height were significantly and negatively correlated with age. Except for the interocular breadth, there were gender differences between males and females in the cephalometric parameters of the three Wa dialect ethnic groups. The cephalofacial features of the Baraoke, A Wa and Wa ethnic groups were different, as evidenced by the fact that males and females of the Baraoke and Wa dialect ethnic group had higher lip height, wider nasal breadth and wider mouth breadth, while males and females of the A Wa ethnic group had lower nasal height.  Conclusion   The cephalofacial features of the three Wa dialect ethnic groups are close to those of the Khmus and Mang, who have their origins in the ancient Baipu people and are also members of the Mon-Khmer language group of the Austroasiatic linguistic. 

Objective To explore the mechanism of action of jolkinolide B in the treatment of gastric cancer by network pharmacology combined with molecular docking technique.   Methods The SwissTargetPrediction database was used to obtain the targets of the active compounds. Search Genecards, OMIM, Drugbank, TTD, and PharmGKB databases to obtain targets for gastric cancer. The intersection between the targets of jolkinolide B and those of gastric cancer was identified pinpoint potential targets for jolkinolide B in treating gastric cancer. The String database was utilized construct a protein-protein interaction(PPI) network. Bioconductor bioinformatics packages with R software was employed conduct Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the shared targets. This process revealed significant regulatory pathways crucial for jolkinolide B’s efficacy in treating gastric cancer. Cytoscape 3.7.1 software was utilized create the core network of “Potential Targets of Triptolide B in Gastric Cancer Treatment”, and SYBYL-X2.1.1 software was employed conduct molecular docking validation of the selected main active ingredients and critical targets.   Results Jolkinolide B may target multiple proteins, including MAPK1, glycogen synthase kinae-3β(GSK-3β), and JUN, impacting the proliferation, invasion, and metastasis of gastric cancer, ultimately inhibiting its growth.     ConclusionWe predicted the possible molecular mechanism of jolkinolide B in the treatment of gastric cancer to provide guide information for the subsequent experimental research and clinical application.

Objective  To investigate the formation and mechanism of dipeptidylpeptidase-4 inhibitor anagliptin inhibiting lung metastasis of colorectal cancer.  Methods   Twenty-four male BALB/c mice were randomly divided into normal group, model group, anagliptin group. The control group did not undergo any treatment. The model group was injected with 0.1 ml CT-26 cells of 109 cells/L. once through the tail vein of the mouse to construct a lung metastasis model, while the anagliptin group was injected intraperitoneally 20mg/(kg·d) 0 day after  constructing a lung metastasis model. The mice were sacrificed after 14 days. HE staining was used to detect the morphological alteration. Determination of CT-26 cell viability through MTT assay and CT-26 cell apoptosis was detected by flow cytometry and live/dead cell staining. Reactive oxygen species(ROS) production was measured by ROS kit. Western blotting was conducted to measure the expression level of Bcl-2, Bax, cleaved-caspase-3, superoxide dismutase(SOD-1) and SOD-2.  Results   HE staining showed that the administration of anagliptin could significantly inhibit the abnormal changes in the model group. Anagliptin inhibited the viability of CT-26 cells above 2 mmol/L. Anagliptin promoted the apoptosis of CT-26 cells. Incubation of anagliptin in CT-26 cells significant promoted the production of ROS. Incubation of anagliptin stimulated the expressions of Bax and cleaved-Caspase-3, while down-regulated the expression of Bcl-2 in CT-26 cells. Administration of anagliptin decreased the expression of SOD-1, but not SOD-2.  Conclusion   Anagliptin promotes apoptosis of colorectal cancer cells and inhibits the formation of lung metastatic tumors through the SOD-1/ROS pathway.  

Objective  To investigate the effect of nobiletin on plateletactivating factor (PAF) metabolism in diabetic rats with renal injury.  Methods   Totally 72 rats were randomly divided into control group (n=10) and modeling group (n=62). The modeling group rats were induced to develop a diabetic rat model with renal injury and then further divided into the model group, aspirin group (20mg/kg), and nobiletin low(50mg/kg), medium(100mg/kg), and high-dose (200mg/kg) groups, each with 10 rats. After continuous oral administration for 6 weeks, rat body weight, kidney weight, and kidney index were measured. Histopathological assessments were conducted by using HE, periodic acid-Schiff staining (PAS), Masson staining, and transmission electron microscopy. Blood glucose levels, renal function, inflammatory factors, PAF and its regulatory factors were detected. Expression levels of PAF metabolism-related proteins, PAF-acetylhydrolase(PAFAH), PAF receptor (PAFR), and cholinephosphotransferase 1(CHPT1) in kidney tissues were assessed using Western blotting and immunohistochemistry.  Results   Following nobiletin intervention, rat body weight increased while kidney weight and kidney index decreased. Improvement in renal tissue pathology was observed, with reduced interstitial fibrosis and thinner basement membrane. Fasting blood glucose and glycated hemoglobin decreased, while fasting insulin showed no significant improvement. Urea nitrogen, blood creatinine, cystatin C, and 24-hour urinary protein excretion were reduced. Levels of interleukin (IL)-1α, IL-6, IL-8, and tumor necrosis factor (TNF-α) were lowered. PAF and its regulatory factors decreased. PAFR and CHPT1 expression decreased, while PAFAH increased.  Conclusion   Nobiletin can alleviate renal injury in diabetic rats with renal injury, improve kidney function, regulate blood glucose, and mitigate inflammatory response. Its mechanism may be associated with the modulation of platelet-activating factor metabolism. 

Objective   To investigate the effects of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in coronary arteriosclerosis (AS) on the migration of stem cell antigen-1(Scal-1) and Nanog positive cells migration.  Methods   Ten atherosclerotic model mice and 10 normal mice were taken respectively, and the fresh hearts of the two groups were taken out, OCT embedding, frozen sections, HE staining and oil red O staining were performed respectively to observe the pathological changes of coronary arteries; Using immunohistochemical staining techniques, the expression changes of TNF-α, IL-6, Scal-1, and Nanog in the coronary artery wall were observed under light microscope. The ventricular tissue of 20 1-week-old mice was excised. Primary Scal-1 and Nanog positive cells were extracted using density gradient centrifugation, and these cells were purified and cultured. Immunofluorescence technology was used to identify the purity of Scal-1 and Nanog positive cells. Transwell migration experiments on passage 1(P1) cells was performed to observe the effects of different concentrations of inflammatory factors on the migration of Scal-1 and Nanog positive cells.  Results  The blood lipid test showed that the total cholesterol, triglycerides, and low-density lipoprotein cholesterol of the model mice were significantly higher than those of the normal control group. Histological staining showed that all the mouse models had obvious coronary atherosclerosis plaque. Immunohistochemical staining results showed that the inflammatory factor TNF-α and IL-6 in atherosclerosis region were strong positive expression, while Scal-1 and Nanog positive cells in atherosclerotic plaques increased, compared to the normal group. The positive rate of Scal-1 in P1 generation cells was about 80%, The positive rate of Nanog was approximately 91%. The Transwell experiment showed that IL-6 had no effect on cell migration at low concentrations, but had an inhibitory effect on cell migration at high concentrations; Low concentrations TNF-α promoted cell migration with 0.5 μg/L TNF-α showing the most significant effection cell migration, and exhibiting inhibitcry effects inhibit at high concentrations.  Conclusion   TNF-α  and IL-6 inflammatory factors, Scal-1 and Nanog positive cells are all involved in the occurrence and development of AS, and the appropriate concentration of inflammatory factors can enhance the migration of stem cells to the coronary atherosclerosis region. 

Objective To investigate the differentiation of oligodendrocyte precursor cells after neural injury utilizing Sox10 cell lineage tracing in the cortical tissue. Methods  C57BL/6 mice and Sox10-CreERT2/red fluorescent protein(RFP) model mice were used in the current study. The Sox10-CreERT2/RFP model mice generated by crossing Sox10-CreERT2 and Ai9 were 8-week-old F1 mice (n =16), which were randomly divided into control group (n =4) and 7 days (n =4), 14 days (n =4), and 30 days feed groups (n =4). Tamoxifen(TAM) was used to induce the expression of RFP. The control group received tamoxifen dissolved in sunflower seed oil by gavage (40 mg/kg once daily for three consecutive days) and the brain tissues were obtained after 4 days. The feed group mice were fed with tamoxifen-containing feed to induce RFP expression, and the brain tissues were obtained after 7, 14, and 30 days, respectively. Immunofluorescent staining was performed to detect the expressions of neuronal nuclei (NeuN), microtubuleassociated protein 2 (MAP2), phosphorylated histone 2AX (γ-H2AX), cluster of differentiation 13 (CD13), γaminobutyric acid (GABA), glial fibrillary acidic protein (GFAP), cluster of differentiation 11b (CD11b), vesicular glutamate transporter 2 (VGLUT2), and adenomatous polyposis coli (APC, CC-1) in the brains of each group mice. The number of positive cells was counted, and the proportion was calculated. Eight-week-old male C57BL/6 mice were randomly divided into wild type(WT) group (n =4) and WT+TAM group (n =4). They were fed with regular feed and tamoxifencontaining feed for 30 days, respectively, and then brain tissues were obtained. Immunofluorescent double-labeling was used to detect the expressions of γ-H2AX positive neurons in the cortex of mice in both groups.   Results  In the control group, feed 7 days,14 days, and 30 days groups, the proportions of RFP⁺ pericytes among all RFP⁺ cells in the cortical tissue were (0.8±0.1)%, (2.7±0.1)%, (3.2±0.1)%, (4.0 ±0.1)%, respectively, and the proportion of mature oligodendrocytes (CC-1⁺ RFP⁺) in the feed 7 days group was (51.2±0.7)%. The proportions of RFPpositive neurons in the cortex after 14 and 30 days of tamoxifen feed were (0.7±0.1)% and (1.5±0.1)%, respectively, while no conversion to RFP-positive neurons was observed in the gavage group and 7 days feed group. RFP cells in the cortex of the 7 days or 30 days feed group did not express GFAP or CD11b. Extensive γ-H2AX⁺ NeuN⁺ staining was observed in the WT group and WT+TAM group. Conclusion  Long-term administration of tamoxifen can promote the differentiation of Sox10 cells into pericytes and neurons. Further investigation into the role of OPC in the neurovascular unit repair mechanism may contribute to a better understanding of the pathogenesis underlying AD. 

Objective To  explore the mechanism of cinobufagin (CBG) in treating gastric cancer based on network pharmacology combined with bioinformatics and molecular docking technology.   Methods Active ingredients and potential targets of CBG in treating gastric cancer were collected from PubChem, TCMSP, and SwissTargetPrediction databases. Transcriptional data of gastric cancer samples were obtained from TGGA database, and gastric cancer-related targets were identified through differential gene analysis. Intersection of targets between CBG and gastric cancer diseases was subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein-protein interaction (PPI) network of common targets was constructed using STRING database, and core targets were selected using Cytoscape software. Molecular docking verification of core targets screened with SYBYL-X 2.1.1 software was conducted with CBG.       Results CBG treatment of gastric cancer involved 59 targets, with 19 key targets identified. Key targets such as aurora kinase A(AURKA), cyclin-dependent kinase 1(CDK1), enhancer of zeste homolog 2(EZH2), hepatocyte growth factor receptor (MET), matrix metallopeptidase 3(MMP-3), progesterone receptor (PGR), prostaglandin-endoperoxide synthase 1(PTGS1), and thymidylate synthase (TYMS) which exhibited good binding activity with CBG and were closely associated with gastric cancer prognosis.    Conclusion CBG may exert anti-gastric cancer effects through multiple targets and pathways.

Objective  To explore the effect of gastrodin（GAS）on the polarization of M2 microglia under oxygen and glucose deprivation（OGD）and the effect of p38 MAPK inhibition on the polarization status of microglia.  Methods BV2 microglia was divided into the control group（Ctrl），p38 MAPK inhibitor SB203580 group（I），OGD group (OGD)，OGD+I group，gastrodin treatment group（G+OGD），and G+OGD+I group. The expressions of p38 MAPK，phosphorylated p38 MAPK（p-p38 MAPK）, M2 microglia marker arginase-1 (Arg-1) and chitinase like protein 1/2（YM1/2）were detected by immunofluorescent staining and Western blotting. Results  Immunofluorescent staining results showed that the pretreatment with gastrodin reduced the fluorescence expression of p-p38 MAPK in OGD induced BV2 microglia, enhanced the fluorescence expressions of Arg-1 and YM1/2. After pretreatment with SB203580，the fluorescence expressions of p-p38 MAPK further decreased，the fluorescence expressions of Arg1 and YM1/2 further increased，both were significantly different from the G+OGD group （ n=3，P<0.05）. The fluorescence expressions of p38 MAPK in each group was not statistically significant（ n=3，P>0.05）. Western blotting results showed that the protein expressions of p-p38 MAPK, Arg-1 and YM1/2 in the OGD group enhanced，compared with that in the control group（ n=3，P<0.05）. After the pretreatment with gastrodin，the protein expression of p-p38 MAPK was reduced significantly，the protein expressions of Arg-1 and YM1/2 was enhanced obviously，both were significantly different from the OGD group （ n=3，P<0.05）. After pretreatment with SB203580，the protein expressions of p-p38 MAPK was further reduced，the protein expression of Arg-1 and YM1/2 were further enhanced，both were significantly different from the G+OGD group（ n=3，P<0.05）. In addition，there was no significant change in p38 MAPK protein expression among groups （ n=3，P>0.05）.  Conclusion  Gastrodin inhibits p38 MAPK signaling activation to promote BV2 microglial polarization towards the M2 phenotype，reducing inflammatory responses and exerting a protective effect. 

Objective To develop a melanoma diagnosis framework based on large-scale vision-language models, and to explore the feasibility and accuracy of the framework for melanoma diagnosis.   Methods The publicly available Derm7pt dataset, which was divided into a training set (346 cases), a validation set (161 cases), and a test set (320 cases) was utilized. A melanoma diagnosis framework based on large-scale vision-language models was proposed, comprising two text branches and one visual branch. In the text branches, one branch processed fixed clinical prompts, while the other handled learnable prompts. This design aimed to optimize the effectiveness of learnable prompts through guidance from fixed clinical prompts. The visual branch processed dermoscopic images and enhanced melanoma feature recognition through fine-tuning the image encoder.   Results On the Derm7pt dataset, our method  outperformd other existing method. It achieved an area under the receiver operating characteristic curve (AUC) of 87.35%, an accuracy of 84.17%, and an F1-score of 84.01%.   Conclusion The study demonstrates that with appropriate fine-tuning strategies, methods based on large-scale vision-language pre-trained models can effectively adapt to melanoma diagnosis tasks. This approach can serve as a powerful auxiliary tool for doctors, helping them make more accurate diagnostic decisions.

Objective  To measure the distal space between skeletal class Ⅲ and skeletal class Ⅰ mandibular molars, compare the differences, and to measure the contact situation between the distal root tip of the second mandibular molar and the lingual cortical bone of the mandible, providing a theoretical reference for the distance of mandibular molar distal movement by using cone beam CT(CBCT).  Methods   CBCT imaging data of 60 adult patients who received orthodontic treatment at Chengde Stomatological Hospital from 2020 to 2022 were selected, including 30 patients with skeletal class Ⅲ mean angle and 30 patients with skeletal class Ⅰ mean angle. CBCT image data were exported to DICOM format, then import it into Mimics 20.0 software, and measure the distal space of bilateral mandibular second molars. The contact between the distal root tip of the second mandibular molar and the lingual bone cortex of the mandible was measured. Import the measurement results into SPSS 19.0 statistical software to analyze the differences and the contact rate.  Results   There was no statistical difference in the measurement results of the distal space of mandibular molars between genders, and sides, and between mandibular molars with or without wisdom teeth (P>0.05). The distal space of mandibular molars in skeletal class Ⅲ were greater than those in skeletal class I, and the difference was statistically significant (P<0.05). The contact rate between the distal root tip of the second mandibular molar and the lingual bone cortex of the mandible was 34.83%. There was no significant difference in the contact rate between the distal root tip of the mandibular second molars and the lingual cortical bone of the mandible between class Ⅲ malocclusion and class I malocclusion(P>0.05).  Conclusion   There is a certain gap in the distal part of the skeletal class Ⅲ mandibular molar. In clinical practice, the molar can be designed to move distally, expanding the dental arch from the sagittal direction to provide a gap for the adduction of the mandibular anterior teeth. However, it is necessary to evaluate the contact between the distal root tip of the second mandibular molar and the lingual bone cortex of the mandible. If the distal root tip of the second mandibular molar contacts the lingual bone cortex of the mandible, the distal movement of the molars should be avoided. 

Objective To observe the difference of bone micro-structure in different regions of proximal femur, micro-CT scanning was performed on 30 proximal femur specimens to explain the mechanism of proximal femur fracture and to provide anatomical basis for prosthesis design.     Methods Totally 30 intact proximal femur specimens were obtained from 60-80 year-old cadavers. Micro-CT scanning was used to measure the trabecular thickness(Tb.Th), trabecular number(Tb.N), trabecular space(Tb.Sp), connectivity(Conn) and bone mineral density(BMD) and other parameters in 7 regions of proximal femur, including proximal pressure trabecular(PPT), distal pressure trabecular(DPT), femoral head-neck junction(FHNJ), head and neck of femoral neck(HNFN), the base of femoral neck(BPFN), intertrochanteric line(IL) and greater trochanter(GT).    Results The bone mineral density of IL and GT were higher than those of BPFN, FHNJ, DPT and PPT. The trabecular thickness of GT was the largest, followed by IL, BPFN and HNFN, and the smallest was FHNJ, DPT and PPT. The trabecular space of IL was larger than that of GT, and the data of both were larger than those of other parts, among which DPT and PPT were the smallest. The trabecular number of IL and GT were the smallest, BPFN, HNFN and FHNJ were larger, and DPT was the largest. The volume fraction of IL was the smallest, BPFN and HNFN were larger, DPT and PPT were the largest.     Conclusion The bone density, trabecular thickness, bone volume, and total volume of GT and IL in the proximal femur of elderly patients are all relatively large, so the reason for the high incidence of fractures is not due to weak internal bone microstructure; The bone density, trabecular thickness, and trabecular gap at the proximal and distal ends of the vertical trabecular bone are relatively small. If it is necessary to perform core decompression for prosthesis filling at this location, the design should be conducive to the mechanical conduction of the prosthesis and the regeneration of surrounding bone tissue.

Objective To investigate the related mechanism which metformin inhibited the proliferation of HCT116 colorectal cancer cells via down-regulating the expression of up-frameshift protein 1 (UPF1).     Methods TCGA and UALCAN databases were utilized to analyze the expression level of UPF1, while Western blotting and Real-time PCR were performed to validate the differences of UPF1 expressions in colon cancer tissues and adjacent normal tissues. Clone formation assay, CCK-8 assay, wound healing assay and Transwell invasion assay were used to examine the effects of knockdown UPF1 on the proliferation, migration and invasion of HCT116 cells respectively. The HCT116 cell dataset with UPF1 knockdown was screened from GEO database for Kyoto Encydopedia of Genes and Genomes(KEGG) pathway analysis, the expression level of differential genes that enriched in Hippo pathway were verified by Real-time PCR. The HCT116 cells were treated with metformin, Western blotting and Real-time PCR were employed to detect the UPF1 expression. Mendelian randomization analysis was performed to explore the causal association between metformin treatment and colorectal cancer.     Results Analysis of TCGA and UALCAN databases showed that both UPF1 mRNA and protein were highly expressed in colon cancer tissues and the expression level of UPF1 was closely correlated with clinicopathologic stage and lymph node metastasis. Compared with adjacent normal tissues, the UPF1 protein and mRNA were highly expressed in colon cancer tissues. Knockdown UPF1 expression could inhibit the proliferation, migration and invasive ability of HCT116 cells. There were 8 differential genes affect the Hippo pathway by KEGG enrichment analysis, Real-time PCR experiments confirmed that CTNNB1, BMP4, TEAD2, PARD6G and FZD1 mRNA decreased in HCT116 cells with UPF1 knockdown. Both UPF1 protein and mRNA expressions decreased after metformin treatment in HCT116 cells. Mendelian randomization analysis showed a negative causal association between metformin treatment and colorectal cancer.      Conclusion Knockdown of UPF1 expression inhibits the proliferation of HCT116 cells through regulating Hippo pathway. Metformin can reduce the UPF1 expression for further inhibiting the proliferation of colorectal cancer cells.

Objective  To investigate the spatiotemporal variations in sexual size dimorphism among Chinese Han students.  Methods  Based on the eight students’physical and healthy investigations, the data on the stature and body mass were systematically collected for 343 928 and 344 029 Chinese Han students aged 19 to 22 years from 1985 to 2019, respectively. The sexual stature dimorphism index (SSDI) and sexual body mass dimorphism index (SBMDI) were employed to analyze the distribution in different periods and regions. In addition, we focused the relationships between these two indices and the per capita consumption expenditure. Results  Positive secular trends were observed in the SSDI and SBWDI among Chinese Han students throughout the 1985 to 2019 period. Notable similarities were identified in the SSDI and SBWDI between northern and southern students. Compared with the SSDI, the SBWDI exhibited significant disparities between urban and rural areas, and demonstrated a positive association with the per capita consumption expenditure.  Conclusion  The female buffering hypothesis possesses a limited range of spatiotemporal adaptability, and the trait more susceptible to environmental influences is better suited to test this hypothesis. 

  浙江大学和中国医学科学院北京协和医学院先后于2012年启动了人脑库建设工作，推动了我国人脑库建设的发展。2014年，“中国人脑组织库建设国际研讨会”在长沙和北京两地成功举办，这次研讨会标志着中国人脑库联盟的初步形成，也意味着我国脑库工作开始正式且系统地展开。此后，我国人脑样本的收集数量显著增加，脑库的建设和管理也日益规范化、专业化［5］。为了进一步促进交流与合作，我国在2014年、2016年、2018年和2022年连续举办了四届“中国人脑组织库建设研讨会”。特别是在2016年，中国人脑组织库协作联盟正式成立，这一联盟为我国各人脑库提供了一个共同交流和协作的平台。随着我国“脑计划”的深入推进，联盟成员已由最初的10家医学院校扩展至现今的27家成员单位，共同助力中国人脑组织库的发展壮大［2］。 

    近年来，随着我国“脑计划”的展开，人脑库的建设也逐渐加速。然而，与国内庞大的科研需求相比，人脑组织库的规模和质量仍有待提升。在人脑组织库的建设中，脑组织的收集数量固然重要，但更为核心的是确保脑组织的质量。高质量的脑组织样本是神经科学研究得以深入进行的基石，它直接关系到研究成果的可靠性和有效性。中国人脑组织库标准化操作方案（standardized operating protocols, SOP）是人脑库建设的重要成果之一，它规范了人脑组织样本的收集、处理、保存和共享的各个环节，确保样本的可靠性和一致性。截至目前，为了满足神经科学领域不断发展的需求，中国人脑组织库协作联盟已经成功制定SOP（2017版）［6，7］并更新（2022版）［8］，同时还推出了一版脊髓取材SOP［9］，以适应神经科学领域的发展需求。中国人脑组织库协作联盟定期开展培训和交流活动，确保各成员单位能够熟练掌握SOP并正确应用于实际工作中。27家脑库联盟成员单位以国家发育和功能人脑组织资源库（中国医学科学院基础医学研究所）、国家健康和疾病人脑组织资源库（浙江大学）、中南大学湘雅医学院人脑组织库和复旦大学上海医学院人脑组织库为核心单位，成立了覆盖全国的人脑组织库协作共建网络，各成员单位及研究人员在人脑组织样本的收集、共享与应用方面做出了重要贡献［10，11］。以河北医科大学人脑组织库为例，该脑库是最早一批加入“中国人脑组织库协作联盟”的单位之一，自2019年成为国家发育和功能人脑组织资源库共建单位以来，已收集保存人脑样本30例，并按照中国人脑组织库标准化操作方案进行了取材、整理及测定等相关工作。 

  河北医科大学人脑组织库2019年12月~2024年2月间收集的30例捐献者样本进行了深入分析和总结，所有工作均严格遵循中国人脑组织库标准化操作方案的指导原则。首先，河北医科大学人脑组织库在样本收集方面展现了高效的组织管理与执行能力。通过对收集样本的统计分析，我们可以看到捐献者的基本信息，如性别、年龄和死亡原因等，这为后续的科学研究提供了重要的参考依据。其次，死亡后取材延误时间较短，12 h 以内的样本占 90%，保证了样本的新鲜度和研究价值。同时，样本的RNA完整性较好，脑脊液pH值稳定，这为后续的分子生物学和病理学研究提供了坚实的基础。 

  在建设过程中，河北医科大学人脑组织库特别强化了病理评估和诊断环节，这是确保人脑样本质量与研究可靠性的核心要素。为了提升病理评估的准确性，河北医科大学人脑组织库派遣工作人员前往荷兰脑库访问，学习并引进其先进的病理诊断技术，现已经建立了11种病理诊断染色技术（如基础染色 HE，特殊染色 Gallyas、Bielschoesky、Congo Red组织学染色，Aβ、p-tau、p-TDP43免疫组织化学染色等），并且能准确诊断多种脑病理疾病（包括阿尔茨海默病、帕金森病、多系统萎缩和皮质基底节变性等）。为了进一步促进国内外脑库与研究机构之间的合作与交流，河北医科大学人脑组织库在2023年成功承办了“第1期人脑组织库样本神经病理诊断阅片培训班”，通过共享数据、技术和经验交流，不断提升病理评估和诊断水平，同时也为人脑科学研究领域做出了积极贡献。 

    随着我国“脑计划”的深入推进，人脑库在国内神经科学研究领域的重要性日益凸显。通过标准化操作和对病理评估与诊断的不断强化，我国人脑组织库正努力提供高质量的研究样本，助力科学家们深入探索大脑的奥秘，这不仅体现了我国在科研领域的实力和决心，也展示了对人类健康与疾病研究的高度重视。我们期待，随着我国人脑库的持续发展和完善，其将为世界神经科学研究贡献更多中国智慧和中国方案，进一步推动人类对大脑和神经系统的认知，为神经系统疾病的预防和治疗提供更有效的策略。

Objective  To construct a three-dimensional statistical shape model of the pelvis and analyze the individual variation and gender differences of the three-dimensional shape of the pelvis. Methods  We collected CT data from 201 Chinese individuals and used deep learning to automatically reconstruct three-dimensional models of the pelvis. Through three-dimensional model registration, dense correspondence mesh mapping, and the use of statistical shape modelling (SSM) and principal component (PC) analysis method, we extracted models of variations (MoV) of pelvic shape changes and statistically compared the shape MoV between males and females. Results  We analysed the top 10 principal components of shape variations, which accounted for 86.1% of the total variability. Among them, PC01, PC02, and PC04 showed significant differences between genders (P <0.001), accounting for a total variability of 60.1%. PC08 and PC10 demonstrated pelvic asymmetry, accounting for a total variability of 3.8%. Conclusion  We constructed a three-dimensional statistical shape model of the pelvis in Chinese individuals, revealing the morphological variation and sex differences of Chinese pelvis.  

Objective To initially explore the possibility of applying the fluorescence micro-optical sectioning tomography (fMOST) high-resolution 3D reconstruction system to the morphological study of the intestinal nervous system and to preliminarily establish a method  for studying the morphology of the intestinal nervous system using this system.    Methods fMOST high-resolution 3D reconstruction system was used to study the intestinal nervous system of C57BL/6 mice in detail. Based on this method, a new morphological method  of the visceral nervous system of small animal models was explored at the single-cell level.   Results Compared with the large intestine, the small intestine lacked the typical myenteric plexus (Auerbach), deep mucosal plexus (Henley), and submucosal superficial plexus (Meissner).   Conclusion The result  of this paper provide a clearer and systematic display of the anatomical structure of the enteric nervous system in C57BL/6 mice, and further clarify the similarities and differences between the enteric nervous system of mice and human, and provide a theoretical basis for its rational application in the study of digestive system diseases. The morphological study of fMOST high-resolution 3D reconstruction system is not limited to the central nervous system, but can be extended to the morphological study of multiple visceral nervous systems.

Objective To identify differentially expressed genes (DEGs) during the early stage of differentiation of human embryonic stem cells (hESCs) into insulin-producing cells (IPCs) and construct the microRNA(miRNA)-mRNA regulatory network.   Methods The datasets GSE42094 from Gene Expression Omnibus (GEO) were employed in this study and included hESCs, Diff1, Diff2, Diff3, Diff4 and IPCs groups. DEGs in the Diff1 group were selected and gene ontology(GO) and Keyoto Encyclopedia of Genes and Genomes(KEGG) pathway were deciphered. The miRNAs associated with DEGs were predicted and the miRNAmRNA regulatory network was visualized. Then the predicted miRNA was validated by paper result.   Results GO result  demonstrated that the significant term of biological process were “cell migration involved in gastrulation” and “SMAD protein signal transduction”. The KEGG pathway analysis indicated that “transformating growth factor(TGF)-beta signaling pathway” and “Signaling pathways regulating pluripotency of stem cells” played essential roles for 28 DEGs in the Diff1 group. To predict miRNA associated with DEGs, we found that miR-335-5p may regulate expressions of CDA, IFITM1, FREM1, FGF17 and ROR2 genes. There were 26 miRNAs which were validated by result  of paper.    Conclusion The miRNA-mRNA regulatory network plays an essential role during the early stage of the induction of IPCs. 

Objective   To explore the regulatory mechanism of non-structural maintenance of chromosome condensin I complex submit G (NCAPG) on proliferation, migration, and invasion of ovarian cancer cells.  Methods   The bioinformatics database was used to analyze the differential expression of NCAPG in ovarian cancer tissues. Western blotting was used to detect the protein expression of NCAPG in normal ovarian epithelial cells IOSE80, ovarian cancer A2780 and SKOV3 cells. The silencing experiments of NCAPG siRNA were divided into blank, control, siNCAPG-1 and siNCAPG-2 groups. The overexpression experiments of NCAPG plasmid were divided into blank, control, NCAPG, NCAPG+MK2206 and MK2206 groups. MTT assay was used to detect cell proliferation activity. Cell scoring assay and transwell assay were used to analyze cell migration and invasion. The protein expressions of p-Akt, total(t)-Akt, proliferative cellular nucleus antigen (PCNA), matrix metallopeptidase 9 (MMP-9), vimentin, N-cadherin, and E-cadherin were detected by Western blotting.  Results   NCAPG was highly expressed in ovarian cancer tissues and cells. Knockdown of NCAPG significantly inhibited the proliferation, invasion and migration of ovarian cancer SKOV3 cells. The protein expressions of p-Akt, PCNA, MMP-9, vimentin and N-cadherin decreased while E-cadherin expression increased. Overexpression of NCAPG significantly promoted the proliferation, invasion and migration of ovarian cancer A2780 cells. The protein expressions of pAkt, PCNA, MMP-9, vimentin, and N-cadherin increased while E-cadherin expression decreased. Akt inhibitor MK2206 significantly attenuated the above effects of NCAPG.  Conclusion  NCAPG promotes the proliferation, invasion, and migration of ovarian cancer cells by activating the Akt signaling pathway and regulating the expression of PCNA, MMP-9, and epithelial-mesenchymal transition (EMT)-related proteins. 

Objective  To investigate the infiltration of peripheral monocyte in the hippocampal CA3 area in neuralgia mice at different time points and explore the effects of the infiltration on neuralgia and the neuralgia-induced anxiety-like behavior in mice. Methods  The healthy male C57 mice were randomly divided into four groups: sham, sciatic nerve branch selective injury（SNI）model （SNI）, CCR2 inhibitor RS102895 (SNI + RS102895) and microglial inhibitor minocycline (MC) (SNI + MC) groups. Both the sham and SNI groups were further divided into 7 days, 14 days and 18 days groups, and the SNI + RS102895 and SNI + MC groups were sampled on the 18th day. Neuralgia was induced by SNI, and mechanical hyperalgesia was assessed by paw withdrawal threshold (PWTs) at different time points. Elevated plus maze (EPM) and open field test (OFT) were performed respectively two days and one day before sacrifice. Immunofluorescence was used to observe the expressions of leukocyte differentiation antigen 45 (CD45) and the co-expression with microglial markers ionized calcium binding adaptor molecule-1(IBA-1), transmembrane protein 119 (TMEM119), astrocyte marker glial fibrillary acidic protein (GFAP), and neuronal marker neuronal nuclei (NeuN) in the hippocampal CA3. The percentage of monocytes in the whole brain of 14 days SNI mice was determined by flow cytometry. Minocycline at 90 mg/(kg·d),  RS102895 at 5 mg/(kg·d) and saline were administered orally on the 5th to 16th day in the corresponding 18 days groups, and the effects of blocking monocyte infiltration on neuralgia and anxiety-like behavior and the expressions of CD45 and IBA-1 in CA3 region of hippocampus were observed.  Results  On the first day after SNI, the PWTs of mice in the 7 days and 14 days groups decreased and continued until before sacrifice( P< 0.01). The CD45 expression did little in the 7 days sham group. Compared with the sham group at the same time point, the CD45 expression did not increase in 7 days SNI mice (P>0.05) and increased significantly in 14 days SNI mice ( P <0.01), only slightly co-expressed with IBA-1 and TMEM119 and no co-expression with GFAP and NeuN, the percentage of monocytes in the whole brain increased significantly in 14 days SNI mice ( P<0.01). Inhibition of microglial activation or CCR2 expression reduced the expression of CD45 in the CA3 in SNI mice (P <0.01), increased the PWTs ( P <0.01) and alleviated anxiety-like behavior in SNI mice (P<0.01).  Conclusion  There was an infiltration of peripheral monocytes in the hippocampal CA3 region after 14 days of SNI-induced neuralgia, which might be involved in the maintenance of neuralgia and the development of neuralgia-induced anxiety-like behaviors. 

Objective To propose a high-precision deep learning-based image assessment method  of osteosarcoma chemotherapy efficacy for clinical treatment, as existing methos have low accuracy of osteosarcoma assessment.   Methods The low incidence of osteosarcoma led to the small scale of its imaging data and the problem of imbalance in data categories. This study combined deep learning with clinical medical information, combined the bone sarcoma generation module of BoneGAN and the scale lesion information capture module, and proposed OMLA-Net, a deep learning assessment network for chemotherapy effect of bone sarcoma based on multi-scale lesion attention network, which achieved computer-aided bone tumor assessment with integrated data augmentation and focused lesion information through pre-training and generalized loss training. Results  In this study, 40 cases of osteosarcoma MRI data were used as the basis for the comparison test on the generated dataset, and the OMLA-Net assessment outperformed the SOTA method  Conv-LSTM-GAN in terms of the assessment effects such as accuracy and F1 scores, and the difference was statistically significant (P<0.05); the subsequent K-fold cross-validation ablation experiments further demonstrated the effectiveness of each module proposed by OMLA-Net.   Conclusion   OMLA-Net can effectively perform the impact assessment of chemotherapy effect on osteosarcoma, which provides a new idea for subsequent clinical application.

Objective  To investigate the biocompatibility of new gadolinium-doped hydroxyapatite (Gd-HA) composite scaffolds and to explore their feasibility as cell culture materials and bone tissue engineering scaffolds.Methods  The Gd-HA composite scaffolds were chemically synthesized and placed under the electron microscope for observation. The experiment was divided into three groups, the HA group, the Gd-HA group, and the control group.Rabbit adipose-derived mesenchymal stem cells (ADSCs) were isolated, cultured and characterized, and the Gd-HA composite scaffold extract was added to the ADSCs in vitro culture system. Cell survival and cytotoxicity were assessed by live-dead cell staining, cell proliferation ability within the scaffolds was assessed by CCK-8 assay, and the scaffolds were assessed by alizarin red staining for cell osteogenic differentiation. The toxic reactions of the scaffold materials were observed by skin irritation test, systemic acute toxicity test and muscle tissue and liver and kidney pathology at the site of intramuscular implantation of the scaffolds.  Results  The Gd-HA composite scaffold showed irregular void structure under electron microscope. Cell morphology observation showed that ADSCs grew adherently to the wall and were long shuttle-shaped. The positivity rate of CD29 was 96.94%, CD44 was 97.90%, CD45 was 0.10%, and CD34 was 0.46%, which was obtained using flow cytometry. Live-dead cell staining showed that the amount of live cells in the Gd-HA group was significantly better than that in the hydroxyapatite(HA) group after 5 days of co-culture. CCK-8 assay showed no significant difference in cell proliferation within 0-3days. After 3days, the Gd-HA group was significantly better than the HA group and the control group (P<0.05). Calcium nodule deposition after alizarin red staining was significantly better in the Gd-HA group than in the HA and control groups, showing a deeper red color. No skin irritation was observed in gross and skin tissue HE observations after the contact of the extract with the skin. The general condition of the experimental groups was good after the infusion of the extract into the abdominal cavity, and the body mass tended to increase steadily (P>0.05). HE staining showed that inflammatory reaction at the interface between the material and muscle tissue of the stent intramuscular implantation site in Gd-HA group was significantly higher than that of the control group, and the inflammatory cell infiltration was gradually reduced with the prolongation of implantation time. At the 8th weeks the morphology of the tissue around the material was close to normal muscle tissue, and no pathological changes were observed in the HE staining of liver and kidney at the 12th week. Conclusion   Gd-HA composite scaffolds exhibit good biocompatibility and facilitate cell proliferation and osteogenic differentiation, and they are expected to serve as good carriers for stem cell transplantation in tissue engineering. 

Homeobox(HOX) genes encode a group of proteins that are highly conserved and closely related to the axial differentiation of embryos. The disorder of segmental development caused by HOX genes deficiency or abnormal expression has been observed in drosophila and mice. However, subsequent studies have found that proteins encoded by the HOX gene family are also involved in the regulation of tumor genesis and development. The roles of the whole HOX family had been reviewed by the author in the past, and through the in-depth researches, the author paid attention to the pivotal role of HOXB9 and made new progress in the study of post-translational modifications of this protein. Taking HOXB9 as a clue, this review summarizes the tumor-related signaling pathways and the modulating effects of post-translational modification of HOXB9 on tumor progression, as well as the possible research directions in the future.

 Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor of the central nervous system in adults, with a median survival of less than 15 months. The tumor microenvironment (TME) of GBM includes extracellular matrix and a variety of immune cells, including tumor-associated macrophages, microglia and myeloid-derived suppressor cells. The interaction between these cells and tumor cells plays a key role in the occurrence and development of GBM. The heterogeneity of GBM microenvironment is one of the main reasons for the poor efficacy of many therapies. Therefore, understanding the interaction between GBM and its tumor microenvironment is helpful to explore new targeted therapeutic strategies, which is expected to provide better treatment options for patients, thereby improving patient prognosis.

Objective To explore whether creatine therapy regulates neuronal ferroptosis by inhibiting the activation of STAT1 signaling pathway associated with suppressor of cytokine signaling 1 (SOCS1) in Alzheimer’s disease.   Methods  Immunohistochemical staining and counting of positive results using paraffin sections of human brain frontal lobes were employed to determine the trend of changes in the target proteins. Further validation was performed by immunofluorescence and Western blotting. STAT1 phosphorylation was inhibited by creatine injection using eleven FAD4Tmice and by cerebellar medullary pool puncture, and the expression of target proteins was examined by immunohistochemistry and immunofluorescence after postmortem sampling.   Results  Compared with the age controls, interferon-γ (IFN-γ), an activating cytokine of the STAT1 signaling pathway, and SOCS1, a negative regulator of STAT1 activation, were both significantly up-regulated, STAT1 phosphorylation was enhanced, and the ferroptosis markers ferritin light chain (FTL) and cystine/glutamate transporter(xCT) increased markedly in the cortex of AD human brains; Creatine treatment of FAD4Tmice resulted in a reduction of both IFN-γ and SOCS1, and a significant decrease in the ferroptosis markers FTL and xCT (SLC7A11).  Conclusion  Creatine ameliorates neuronal ferroptosis in AD model mice by reducing neuronal STAT1SOCS1 signalling activation. 

 Integrins are transmembrane receptors that can coordinate signal transduction between cells and extracellular matrix or between cells. The abnormal function of integrins is one of the recognized mechanisms of tumor development. As an important regulatory mode, post-translational modification can change the conformation and physicochemical properties of proteins, thus affecting their activities, stability and functions. After the modification of the integrin, such as glycosylation and methylation, the corresponding signal transduction pathway changes, and then affects cell adhesion, migration, differentiation and other life activities, involving in diverse physiology and pathological processes. Post-translational modifications of integrins are abundant in tumor progression and play a key role in regulating the growth, metastasis and drug resistance of different tumor cells. In this review, the structure and function, post-translational modification of integrins, and their relationship with occurrence and development of tumors will be discussed, in order to provide more explorable targets for the treatment of cancer.

Objective  To study the effect of reactive oxygen species (ROS)/p38 MAPK cascade reaction on the formation of kidney stones (KS) in rats and explore the mechanism.  Methods   Fifty SD rats were randomly divided into control group (normal feeding), N-acetylcysteine (NAC) group (intraperitoneally injected 200 mg/kg NAC), KS group (constructed calcium oxalate KS model), KS+NAC group (constructed calcium oxalate KS model, intraperitoneally injected 200 mg/kg NAC), KS+NAC+tunicamycin (TM) group(constructed calcium oxalate KS model, intraperitoneally injected 200 mg/kg NAC and 1 mg/kg TM), with 10 rats in each group. After 4 weeks of administration, 24 hours urine volume and oxalic acid (Ox) of each group were measured, serum creatinine (Cr), urea nitrogen (BUN) and uric acid (UA) levels were detected by automatic biochemical analyzer. HE staining and Von Kossa staining were used to observe the histopathological changes and crystal deposition of the kidney. TUNEL staining was used to detect apoptosis of renal tissue cells. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in renal tissue were measured by the kit. DHE fluorescent probes detected the levels of reactive oxygen species (ROS) in kidney tissue. Immunohistochemical staining was used to detect the expressions of microtubule-associated protein 1 light chain 3 B (LC3B) and glucose regulatory protein 78 (GRP78) in renal tissue, and the protein expression of LC3Ⅱ/LC3Ⅰ, Beclin1, GRP78, CCAAT/enhancer binding protein homologous protein (CHOP) in renal tissue was determined by Western blotting.  Results   Compared with the KS group, Ox in KS+NAC group decreased (P<0.05), BUN, Cr and UA levels decreased (P<0.05), renal tubule dilatation and calcium oxalate crystallization decreased, TUNEL positive cell rate decreased (P<0.05), SOD activity increased and MDA content decreased (P<0.05), ROS levels decreased (P<0.05), LC3B and GRP78 positive staining levels decreased (P<0.05), the relative protein expressions of p-p38 MAPK/p38 MAPK, LC3Ⅱ/LC3Ⅰ, Beclin1, GRP78 and CHOP were down-regulated(P<0.05). Compared with the KS+NAC group, Ox in KS+NAC+TM group increased (P<0.05), BUN, Cr and UA levels also increased (P<0.05), renal tubule dilated significantly, calcium oxalate crystals increased, TUNEL positive cell rate increased (P<0.05), SOD activity decreased and MDA content increased (P<0.05), ROS levels increased (P<0.05), LC3B and GRP78 positive staining levels increased (P<0.05), the relative protein expressions of p-p38 MAPK/p38 MAPK, LC3Ⅱ/LC3Ⅰ, Beclin1, GRP78 and CHOP were also up-regulated (P<0.05).  Conclusion   ROS/p38 MAPK cascade is involved in promoting KS formation in rats, which is related to the activation of endoplasmic reticulum stress-mediated autophagy pathway. 

 Human brain banks use a standardized protocol to collect, process and store post-mortem human brains and related tissues, along with relevant clinical information, and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols (SOP). Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders, highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples. The first version of SOP in 2017 was published by the China Human Brain Bank Consortium. As members increases from different regions in China, a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research. The revised SOP places a strong emphasis on ethical standards, incorporates neuropathological evaluation of brain regions, and provides clarity on spinal cord sampling and pathological assessment. Notable enhancements in this updated version of the SOP include reinforced ethical guidelines, inclusion of matching controls in recruitment, and expansion of brain regions to be sampled for neuropathological evaluation.

Objective To construct a mouse model of alcoholic liver fibrosis and explore the effect of supplementing exogenous thyroid hormone T3 on oxidative stress in liver. Methods  Eighty mice were randomly divided into 6 groups, normal control group, alcoholic liver fibrosis(ALF) model group, and low concentration T3 intervention group (25 μg/kg), medium concentration T3 intervention group (50 μg/kg), high concentration T3 intervention group (100 μg/kg) and T3 control group (the concentration of T3 is 100 μg/kg). A model of mice alcoholic liver fibrosis was established by using alcoholic liquid feed combined with 31.5% ethanol gavage. From the sixth week, mice in the T3 intervention and T3 control group were injected with corresponding concentrations of T3 intraperitoneally for three weeks. Mice in the control and T3 control groups were fed with control liquid feed. The degree of mice liver injury and fibrosis was evaluated through the sirius red staining, Western blotting, and serum biochemical testing. The activity of superoxide dismutase(SOD), the content of glutathione(GSH) and malondialdehyde(MDA) in liver tissue were detected by ELISA, and the protein expressions of microtubule-associated protein light chain 3-Ⅱ(LC3-Ⅱ) and p62 were detected by immunohistochemistry and Western blotting. Results  The liver structure and function in the ALF group were severely damaged, autophagy was inhibited, and the oxidative stress response was significantly enhanced compared with the control group. Compared with the ALF group, the recovery of liver functional and structure and autophagy were showed in the T3 intervention group, and SOD activity and GSH content in the liver increased in the low and medium concentrations of T3 intervention groups, while MDA content significantly decreased. In the high concentration T3 intervention group, it showed the same increase in SOD activity, a significant decrease in MDA content, while the content of GSH was lower than that in the control group, which was not different with the ALF group. Conclusion  Appropriate supplementation of T3 could affect the occurrence and development of alcoholic liver fibrosis by restoring the liver autophagy to inhibit the oxidative stress response. 

Objective  To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts (RAGE) of astrocytes after hypoxicischemic brain damage(HIBD) in neonatal rats and the effects of gastrodin (GAS) intervention on them. Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group, HIBD group and HIBD+GAS group(100 mg/kg), and the expressions of A1 type astrocyte marker C3, A2 type astrocyte marker S100A10, RAGE, tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor(BDNF), and insulin-like growth factor(IGF-1) in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group, oxygen glucose deprivation(OGD) group, OGD+GAS (0.34mmol/L) group and GAS group, and then the protein expressions of RAGE, TNF-α, BDNF and IGF-1 were detected by Western blotting and immunofluorescence. Results  In vivo, Western blotting showed that compared with the sham group, the protein expression levels of C3, S100A10, RAGE, TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group (P <0.05), but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group (P <0.05). Compared with the HIBD group, the C3, RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group (P <0.05), and the protein expression levels of BDNF and IGF-1 further increased(P<0.05). The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment (P<0.05). The immunohistochemical staining results of C3, S100A10, and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results. Furthermore, the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes (P<0.05). After GAS intervention, while the expressions of both RAGE and TNF-α decreased significantly (P<0.05), the expressions of BDNF and IGF-1 increased significantly (P<0.05). Conclusion  With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors, gastrodin can promot the expressions of A2 astrocyte and nutritional factors, which play an important role in neuro-protective effect.